Alogliptin, 2-({6[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl}methyl)benzonitrile, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is an anti-diabetic drug which is approved in US as monotherapy or combination therapy with other agents such as metformin, sulfonylurea, thiazolidinedione and insulin, for improving glycemic control in adults with type 2 diabetes mellitus.
Metformin, N,N-Dimethylimidodicarbonimidic diamide, is an anti-diabetic drug belonging to biguanide class and is approved in US for monotherapy or combination therapy with other agents such as sulfonylureas, thiazolidinediones, meglitinides, DPP-IV inhibitors and SGLT2 inhibitors, for improving glycemic control in adults with type 2 diabetes mellitus.
U.S. Pat. No. 8,900,638 discloses therapeutic combination for diabetes or obesity; comprising dipeptidyl peptidase (DPP-IV) inhibitor alogliptin or a salt thereof and Metformin HCl; wherein alogliptin or a salt thereof and metformin HCl are physically separated from each other to provide stability to the formulation. It further describes the solid composition wherein contact of alogliptin or a salt thereof and metformin HCl is inhibited by layering approaches or by forming granules of alogliptin or a salt thereof and metformin HCl separately using wet granulation process.
Composition of alogliptin and metformin is either associated with manufacturing complexities such as sticking with alogliptin and incompatibility of alogliptin and metformin with each other or some of the excipients, which affects stability and dissolution of the formulation. The available prior art though tried to overcome problem of decrease in preservation stability by following different method of manufacturing such as different layering approaches or formulating granules of alogliptin and metformin separately with purpose of inhibiting contact of alogliptin and metformin; these techniques with added steps are tedious leading to increased complexity of manufacturing. Thus, there still remains need for development of stable pharmaceutical composition of alogliptin and metformin devoid of processing troubles with ease of manufacturing.
Present invention provides a stable, bioequivalent composition of alogliptin and metformin which overcomes all the mentioned issues and is produced using robust, reproducible and easily scalable process.